title: Insights from studies with oral cleft genes suggest associations between WNT-pathway genes and risk of oral cancer.
abstract: Oral squamous cell carcinoma (OSCC) accounts for more than 90% of the malignant neoplasms that arise in the mucosa of the upper aerodigestive tract. Recent studies of cleft lip/palate have shown the association of genes involved in cancer. WNT pathway genes have been associated with several types of cancer and recently with cleft lip/palate. To investigate if genes associated with cleft lip/palate were also associated with oral cancer, we genotyped 188 individuals with OSCC and 225 control individuals for markers in AXIN2, AXIN1, GSK3β, WNT3A, WNT5A, WNT8A, WNT11, WNT3, and WNT9B. Statistical analysis was performed with PLINK 1.06 software to test for differences in allele frequencies of each polymorphism between cases and controls. We found association of SNPs in GSK3B (p = 0.0008) and WNT11 (p = 0.03) with OSCC. We also found overtransmission of GSK3B haplotypes in OSCC cases. Expression analyses showed up-regulation of WNT3A, GSK3B, and AXIN1 and down-regulation of WNT11 in OSCC in comparison with control tissues (P < 0.001). Additional studies should focus on the identification of potentially functional variants in these genes as contributors to human clefting and oral cancer.
authors.affiliation: Department of Otolaryngology and Immunology, Hillman Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Andrade Filho
authors.forename: A
authors.initials: A
authors.lastname: Letra
authors.forename: A
authors.initials: A
authors.lastname: Cramer
authors.forename: J L
authors.initials: JL
authors.lastname: Prasad
authors.forename: G P
authors.initials: GP
authors.lastname: Garlet
authors.forename: A R
authors.initials: AR
authors.lastname: Vieira
authors.forename: R L
authors.initials: RL
authors.lastname: Ferris
authors.forename: R
authors.initials: R
authors.lastname: Menezes
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060466:Axin Protein; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics*; D060508:Wnt3 Protein; D060509:Wnt3A Protein
chemical_list: C555451:AXIN1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; D009363:Neoplasm Proteins; D012097:Repressor Proteins; C555507:WNT3 protein, human; C555510:WNT3A protein, human; D051153:Wnt Proteins; C540523:Wnt11 protein, human; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3